Through my education in physics, I gained experience in the implementation of computer algorithms, the understanding of numerical methods applied to analysis, and the handling of large data samples. I am now bringing these skills to the field of computational biology. In the past 2 years, as a member of the Kruglyak Lab and with support from a DOE/Sloan Foundation fellowship, I have acquired experience in genomics through reading and seminars and through hands-on work on research projects. During the 3 years on the K01 Award I plan to work on three research areas: (1) Computational approaches for rapid multipoint analysis (exact and approximate methods) of qualitative and quantitative traits in large, complex pedigrees. The methods will take advantage of exact symmetries or exactly broken symmetries generated by the observation of genotypes. In cases where a very large number of ancestors is not available for genotyping, I will take advantage of approximate symmetries generated by information lost due to ungenotyped ancestors. (2) Haplotype analysis and multipoint linkage disequilibrium mapping. I will develop computational methods that take advantage of high information content available in dense SNP haplotypes and rigorously assess the probability of haplotype sharing in today's population, given the history of the student subjects. (3) Genetic dissection of regulatory pathways in yeast. I will apply genetics analysis methods to identify genomic regions that regulate RNA transcription in yeast. I will use array experiments to investigate linkage between regulatory regions of the genome and RNA expression levels (the quantitative phenotype) in crosses of similar yeast strains. This is an excellent test bed for the investigation of multi-gene, complex traits and is directly related to my interest in human genetics. My mentor is Leonid Kruglyak. Dr. Kryuglyak earned his Ph.D. in physics and has transitioned successfully to a very productive career in genomics. Together we developed my training plan that includes formal coursework and laboratory training that will allow me to develop into a productive, independent investigator.